Cell division is dependent on mitosis, and relates to cancer development and progression.
Polo-like kinase 1 (Plk1), a serine-threonine kinase, has a key role in the regulation of cell division, including mitotic entry, spindle formation, chromosome segregation, and cytokinesis1-3.
Moreover, downregulation of Plk1 by antisense oligonucleotides and siRNA (small interfering RNA) results in a marked reduction in proliferation and increase in apoptosis in tumor cells, but not in normal cells in vitro, and has been demonstrated to be a powerful suppression of tumor growth in a xenogenic model.
Recently, Several Plk1 inhibitors, including scytonemin, B-2536, HMN-214, ON-01910, and poloxin, are under development as potential treatments for cancer, with some of them in clinical trials.
Many tumor antigens are tolerogenic as self-antigens, it is often difficult to induce a specific immune responses against them. Dendritic cells (DC), as the most potent antigen-presenting cells, can break tolerance against self-antigens by effectively priming naive T cells in vitro and in vivo.
Meanwhile, the molecules that regulate the cell cycle, Aurora A, Topoisomerase II α (Top IIα), Foxm1, and Ran have been reported to be tumor antigens. Aurora A was defined as a novel target of cellular immunotherapy for leukemia.
The immunogenicity of TopIIa was demonstrated in a mouse system by vaccination with mRNA electroporated DCs.
Foxm1 and Ran peptide can induce cytotoxic T lymphocytes (CTL) activity in human PBMC and in human leukocyte antigen (HLA)-A2 transgenic mice.
Plk1 is tightly associated with these proteins as a key cell cycle protein. If P1K1 induced tumor cell-specific immune response, it would be used as a target of immunotherapy for specific removal of tumor cell. However, this tumor cell-specific immune response of P1k1 is not known by now.